crossing96/oncoscreening huggingface dataset:
Presence of detrusor muscle in bladder tumor specimens--predictors and effect on outcome as a measure of resection quality.	OBJECTIVES: To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze its effect on clinical outcome as an indicator of resection quality. METHODS: The bladder cancer database of a tertiary medical center was queried for patients who underwent complete transurethral resection of bladder tumor (TURBT) between 2008 and 2009. Study end points were absence of detrusor muscle in the surgical specimen and its association with disease recurrence/progression. RESULTS: Detrusor muscle in the surgical specimen was found in 265 of the 332 study patients (79%). The likelihood of finding muscle increased with higher clinical stage (Odds Ratio [OR]-1.8), higher tumor grade (OR-3), larger tumor size (OR-3.2), multifocal disease (OR-1.7), and nonpapillary morphology (OR-2.3). History of bladder cancer, surgeon's experience, and tumor location in the bladder had no effect. In the whole study population, neither tumor recurrence nor disease progression was associated with absence of detrusor muscle. In patients with T1 tumors, absence of detrusor muscle in the specimen was associated with higher early recurrence rate but not worse long-term outcome. CONCLUSIONS: Absence of detrusor muscle in TURBT specimens is not determined by the technical difficulty of the procedure or surgical experience. Surgeons are more prone to obtain deep muscle in large, nonpapillary-appearing tumors, likely reflecting efforts to attain accurate staging in these cases. The presence or absence of detrusor muscle may serve as a surrogate of resection quality in patients with T1 tumors, but its general applicability to the overall population of patients undergoing TURBT remains questionable.	bladder
p53-stabilizing agent CP-31398 prevents growth and invasion of urothelial cancer of the bladder in transgenic UPII-SV40T mice.	The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001). A significant decrease in the bladder tumor weights (by 68.6-80.2%, P < .0001 in males and by 36.9-55.3%, P < .0001 in females) was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.	bladder
Effect of laminin 332 on motility and invasion in bladder cancer.	We examined the correlation between laminin 332 and malignancy in bladder cancer patients, and, using a strain of invasive bladder cancer cells, determined whether laminin 332 causes bladder cancer motility and invasion. To investigate the correlation between laminin 332 g2 distribution and patient outcome, we performed a semiquantitative immunohistochemical analysis of 35 paraffin-embedded samples using the antibody D4B5, which is specific for the laminin 5 γ2 chain. To evaluate the role of laminin 332 in NBT-II cell motility and invasion, we used a scratch assay and the Boyden chamber chemoinvasion system. Tumor stage and grade were significantly correlated with a loss of laminin 332 γ2 chain from the basement membrane (p = 0.001) and its retention in the cytoplasm (p = 0.001) (Kruskal-Wallis test). Kaplan-Meier survival curves revealed an association between the risk of progression and cytoplasmic retention of the laminin 332 γ2 chain. In addition, an in vitro scratch assay showed an increase in the migration of cells treated with laminin 332 from their cluster. The Boyden chamber assay showed that laminin 332 potentiated NBT-II cell invasion. Immunohistochemistry results showed that bladder cancer patients with a higher malignancy expressed more laminin 332. The in vitro scratch and invasion assay showed that laminin 332 stimulated the motility and invasion of bladder cancer cells. The invasion assay explains the correlation between laminin 332 expression and bladder cancer malignancy.	bladder
Risk of in-hospital complications after radical cystectomy for urinary bladder carcinoma: population-based follow-up study of 7608 patients.	OBJECTIVE: To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy (RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer (UBC). PATIENTS AND METHODS: In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008. We estimated the frequency and incidences and calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards models. RESULTS: Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years. There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir (HR: 1.11 (0.94-1.30) or orthotopic neobladder 1.21 (1.05-1.39) than among those with ileal conduit. Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure. In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit (HR: 0.64 (0.50-0.81)) and those with continent cutaneous reservoir (HR: 0.92 (0.73-1.16). CONCLUSIONS: In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients. Comparison between different types of diversion should, however, be made with care because of potential confounding by indication.	bladder
NBI cystoscopy and bipolar electrosurgery in NMIBC management - An overview of daily practice.	"INTRODUCTION: The standard non-muscle invasive bladder cancer (NMIBC) endoscopic diagnosis suffers from the frequently unsatisfactory white light evaluation accuracy leading to residual lesions being left behind. Monopolar transurethral resection of bladder tumors (TURBT) is marked by a substantial morbidity rate requiring further amelioration. METHODS: Small size tumors (under 1 cm) are feasible for ""en bloc"" resection. Bipolar TURBT was defined as being able to challenge the gold-standard status of monopolar resection due to the reduced complication rates. Plasma-button vaporization was introduced as a promising large bladder tumors' ablation modality. Narrow band imaging (NBI) cystoscopy became an increasingly popular method of enhancing tumor detection. RESULTS: The ""en bloc"" resection of small size or thin pedicle tumors provides the conditions for avoiding tumoral tissue scattering. Bipolar resection is characterized by decreased perioperative bleeding risks and faster patient recovery. Plasma-button vaporization gained confirmation as an innovative approach, able to dispose large tumor bulks under complete control while minimizing the associated morbidity. NBI cystoscopy is a useful tool in identifying CIS lesions, small papillary tumors or extended margins of large tumor formations. As a cost-free technique, it may be extensively used both during the NMIBC initial diagnostic as well as during follow-up evaluation protocol. CONCLUSIONS: Having in mind the various modalities of ameliorating the bladder cancer diagnostic and treatment, NMIBC management should be tailored in accordance with the particularities of each case."	bladder
Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer.	PURPOSE: We sought to define the prevalence and co-occurrence of actionable genomic alterations in patients with high-grade bladder cancer to serve as a platform for therapeutic drug discovery. PATIENTS AND METHODS: An integrative analysis of 97 high-grade bladder tumors was conducted to identify actionable drug targets, which are defined as genomic alterations that have been clinically validated in another cancer type (eg, BRAF mutation) or alterations for which a selective inhibitor of the target or pathway is under clinical investigation. DNA copy number alterations (CNAs) were defined by using array comparative genomic hybridization. Mutation profiling was performed by using both mass spectroscopy-based genotyping and Sanger sequencing. RESULTS: Sixty-one percent of tumors harbored potentially actionable genomic alterations. A core pathway analysis of the integrated data set revealed a nonoverlapping pattern of mutations in the RTK-RAS-RAF and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways and regulators of G1-S cell cycle progression. Unsupervised clustering of CNAs defined two distinct classes of bladder tumors that differed in the degree of their CNA burden. Integration of mutation and copy number analyses revealed that mutations in TP53 and RB1 were significantly more common in tumors with a high CNA burden (P < .001 and P < .003, respectively). CONCLUSION: High-grade bladder cancer possesses substantial genomic heterogeneity. The majority of tumors harbor potentially tractable genomic alterations that may predict for response to target-selective agents. Given the genomic diversity of bladder cancers, optimal development of target-specific agents will require pretreatment genomic characterization.	bladder
Use of nonsteroidal anti-inflammatory drugs and bladder cancer risk: a meta-analysis of epidemiologic studies.	PURPOSE: Several epidemiologic studies have evaluated the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and bladder cancer risk and the results were varied. Thus, we conducted a comprehensive meta-analysis of studies exclusively dedicated to the relationship between the 3 most commonly used analgesics and bladder cancer risk. METHODS: A systematic literature search up to November 2012 was performed in PubMed database for 3 categories of analgesics: acetaminophen, aspirin or non-aspirin NSAIDs. Study-specific risk estimates were pooled using a random-effects model. RESULTS: Seventeen studies (8 cohort and 9 case-control studies), involving a total of 10,618 bladder cancer cases, were contributed to the analysis. We found that acetaminophen (relative risk [RR] 1.01, 95% confidence interval [CI] 0.88-1.17) and aspirin (RR 1.02, 95% CI 0.91-1.14) were not associated with bladder cancer risk. Although non-aspirin NSAIDs was statistically significantly associated with reduced risk of bladder cancer among case-control studies (but not cohort studies), the overall risk was not statistically significant (RR 0.87, 95% CI 0.73-1.05). Furthermore, we also found that non-aspirin NSAIDs use was significantly associated with a 43% reduction in bladder cancer risk among nonsmokers (RR 0.57, 95% CI 0.43-0.76), but not among current smokers. CONCLUSION: The results of our meta-analysis suggest that there is no association between use of acetaminophen, aspirin or non-aspirin NSAIDs and bladder cancer risk. However, non-aspirin NSAIDs use might be associated with a reduction in risk of bladder cancer for nonsmokers.	bladder
The CCND1 G870A polymorphism and susceptibility to bladder cancer.	Published studies on the association between cyclin D1 (CCND1) G870A polymorphism and bladder cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of G870A polymorphism and bladder cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manager 5.0 and Stata 11.0. Significant association between G870A polymorphism and bladder cancer susceptibility was found under recessive model in overall population (OR = 1.21, 95% CI 1.01-1.45, P = 0.04). When stratifying for the race, our analysis suggested that CCND1 G870A was associated with bladder cancer risk in Asians when using homogeneous codominant (OR = 1.72, 95% CI 1.34-2.20, P < 0.0001), recessive (OR = 1.46, 95% CI 1.21-1.77, P < 0.0001), dominant (OR = 1.36, 95% CI 1.10-1.69, P = 0.004), and allelic models (OR = 1.30, 95% CI 1.15-1.47, P < 0.0001) to analyze the data. However, no significant associations were found in Caucasians. After stratifying the studies by control source, G870A polymorphism was significantly associated with bladder cancer risk under recessive model (OR = 1.31, 95% CI 1.03-1.67, P = 0.03) in hospital-based case-control studies, but not in population-based case-control studies. This meta-analysis suggested that G870A polymorphism most likely contributes to increased susceptibility to bladder cancer in the overall population, hospital-based case-control studies, and Asians.	bladder
Immunohistochemical cellular distribution of proteins related to M phase regulation in early proliferative lesions induced by tumor promotion in rat two-stage carcinogenesis models.	We have previously reported that 28-day treatment with hepatocarcinogens increases liver cells expressing p21(Cip1), a G1/S checkpoint protein, and M phase proteins, i.e., nuclear Cdc2, Aurora B, phosphorylated-Histone H3 (p-Histone H3) and heterochromatin protein 1α (HP1α), in rats. To examine the roles of these markers in the early stages of carcinogenesis, we investigated their cellular distribution in several carcinogenic target organs using rat two-stage carcinogenesis models. Promoting agents targeting the liver (piperonyl butoxide and methapyrilene hydrochloride), thyroid (sulfadimethoxine), urinary bladder (phenylethyl isothiocyanate), and forestomach and glandular stomach (catechol) were administered to rats after initiation treatment for the liver with N-diethylnitrosamine, thyroid with N-bis(2-hydroxypropyl)nitrosamine, urinary bladder with N-butyl-N-(4-hydroxybutyl)nitrosamine, and forestomach and glandular stomach with N-methyl-N'-nitro-N-nitrosoguanidine. Numbers of cells positive for nuclear Cdc2, Aurora B, p-Histone H3 and HP1α increased within preneoplastic lesions as determined by glutathione S-transferase placental form in the liver or phosphorylated p44/42 mitogen-activated protein kinase in the thyroid, and hyperplastic lesions having no known preneoplastic markers in the urinary bladder, forestomach and glandular stomach. Immunoreactive cells for p21(Cip1) were decreased within thyroid preneoplastic lesions; however, they were increased within liver preneoplastic lesions and hyperplastic lesions in other organs. These results suggest that M phase disruption commonly occur during the formation of preneoplastic lesions and hyperplastic lesions. Differences in the expression patterns of p21(Cip1) between thyroid preneoplastic and proliferative lesions in other organs may reflect differences in cell cycle regulation involving G1/S checkpoint function between proliferative lesions in each organ.	bladder
Comparative safety analysis of surgical smoke from transurethral resection of the bladder tumors and transurethral resection of the prostate.	OBJECTIVE: To analyze the gas generated from the transurethral resection of the prostate (TURP) and transurethral resection of bladder (TURB) tumor. METHODS: Thirty-six smoke samples were collected from a continuous irrigation suction system during the TURP and the TURB. Then, they were subdivided into 2 groups: the group I (n = 18; gases generated from the TURP) and the group II (n = 18; gases generated from the TURB). We performed qualitative and quantitative analysis of the samples on gas chromatography/mass spectrometry. RESULTS: A more diverse type of gas was generated from the TURB as compared with the TURP. A further quantitative analysis was performed for 7 of 16 gases and 13 of 39 gases in the group I and group II, respectively. This showed that there was no significant difference in the concentration of propylene (propylene: 148.36 ± 207.72 ug/g vs 96.956 ± 135.138 ug/g) and 1-pentene (5137.08 ± 2935.48 ug/g vs 4478.259 ± 5787.351 ug/g) between the TURP and the TURB (P >.05). CONCLUSION: Our results showed that 39 and 16 types of gases were generated from the TURB and the TURP, respectively. There were differences in the types of gases between benign hypertrophic prostate and malignant bladder tumor tissues. This indicates that electrosurgery of malignant tissue is possibly more hazardous to those who are involved in the surgical operation.	bladder
Lymph node dissection during radical cystectomy for bladder cancer treatment: considerations on relevance and extent.	Despite advances in the surgical and medical treatment for urothelial carcinoma of the bladder (UCB), there have only been limited improvements in disease-specific mortality rates over the past decades. Lymph node dissection (LND) during radical cystectomy is an integral part of the treatment for muscle-invasive and high-risk UCB. LND may detect and remove lymph node (LN) metastasis and thus guide patient counseling and decision making regarding additional treatment decisions. In addition, LND may improve survival in patients both with and without LN metastasis. In this non-systematic review article, we discuss benefits and risks of LND, the role of limited versus extended LND and the dilemma of preoperative LN staging.	bladder
Long-term follow-up of patients with tumours of the renal pelvis and ureter: how often is a bladder tumour diagnosed after five tumour-free years?	OBJECTIVE: It is not known when cystoscopy follow-up should be terminated after surgery for tumours of the renal pelvis and ureter [upper urinary tract tumours (UUTTs)]. The aim of this study was to investigate the length of the interval from surgery to diagnosis of the first bladder tumour. MATERIAL AND METHODS: A review was performed of all 930 patients who were diagnosed with a UUTT from 1971 to 1998 in western Sweden. The time to the first bladder tumour was estimated using Kaplan--Meier analyses. Univariate and multivariate analyses of potential risk factors for bladder recurrence were performed. RESULTS: In total, 614 patients were treated surgically for a renal pelvic or ureteral tumour and underwent cystoscopy at least 3 months afterwards. Of these 614 patients,192 (31.3%) patients developed a bladder tumour after the upper tract surgery. The majority, 157 out of 192 patients (81.8%), were diagnosed during the first 2 years, an additional 24 patients (12.5%) during years 3--5 and 11 patients (5.7%) between years 5 and 20. A history of bladder tumours, large tumour diameter, carcinoma in situ and UUTT diagnosed during the last part of the study period were significant risk factors for bladder recurrence after upper tract surgery. CONCLUSION: Cystoscopy should be performed at short intervals during the first 2 years after surgery for a UUTT, in particular among patients with a history of bladder tumours. Late bladder recurrences are unusual; therefore, as a rule, follow-up cystoscopy should be terminated after 5 tumour-free years.	bladder
Does minimally invasive surgery for radical cystectomy provide similar long-term cancer control as open radical surgery?	PURPOSE OF REVIEW: Open radical cystectomy (ORC) and pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive and high-risk nonmuscle-invasive bladder cancer (BCa), but is associated with significant morbidity. In the hope of decreasing the complications and improving the surgical tolerance, minimally invasive techniques to perform radical cystectomy and PLND have been adopted. This review focuses on the present state of the literature regarding the oncological efficacy of minimally invasive radical cystectomy (MIRC) and PLND. RECENT FINDINGS: Most studies are retrospective, single surgeon or institution, and are subjected to significant selection bias. There is scarce data regarding intermediate and long term oncological outcomes following MIRC, and most reported series contain a lower proportion of patients with locally advanced disease compared with ORC series. Positive surgical margin rates are similar between the approaches in localized disease, but may be significantly higher in MIRC in patients with more advanced tumors. SUMMARY: The current review of the literature demonstrates insufficient evidence regarding the long-term oncological outcomes of MIRC. There is a need for well controlled, prospective, randomized trials with sufficient follow-up to compare MIRC to ORC for the treatment of invasive BCa before the oncologic efficacy of these techniques can be adequately compared to the standards established by ORC.	bladder
Inhibition of inducible heat shock protein-70 (hsp72) enhances bortezomib-induced cell death in human bladder cancer cells.	The proteasome inhibitor bortezomib (Velcade) is a promising new agent for bladder cancer therapy, but inducible cytoprotective mechanisms may limit its potential efficacy. We used whole genome mRNA expression profiling to study the effects of bortezomib on stress-induced gene expression in a panel of human bladder cancer cell lines. Bortezomib induced strong upregulation of the inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and SW780 (HSPA1A(high)) cells, but only induced the HSPA1B isoform in UM-UC10 and UM-UC13 (HSPA1A(low)) cells. Bortezomib stimulated the binding of heat shock factor-1 (HSF1) to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation-specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low) cell lines (UM-UC10 and UM-UC13), and exposure to the chromatin demethylating agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72 promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas transient knockdown of HSPA1B further sensitized these cells to bortezomib, and exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo. Together, our results provide proof-of-concept for using Hsp72 inhibitors to promote bortezomib sensitivity in bladder cancers and suggest that selective targeting of HSPA1B could produce synthetic lethality in tumors that display HSPA1A promoter methylation.	bladder